聚(L-谷氨酸)-g-甲氧基聚(乙二醇)/组织死灰木素A4（CA4）/BLZ945纳米粒子（CB-NPs）在协同癌症治疗中显示出巨大的潜力。然而，尚不清楚纳米粒子的配方，如注射剂量，活性剂比例和药物装载含量如何影响CB-NPs的副作用和体内疗效。在此研究中，合成了一系列具有不同BLZ945/CA4（B/C）比例和药物装载含量的CB-NPs，并在肝瘤（H22）带瘤小鼠模型上进行了评估。注射剂量和B/C比例发现对体内抗癌疗效具有显着影响。CB-NPs 20具有0.45/1的B/C重量比和20.7 wt％的总药物装载含量（B + C），显示出最高的临床应用潜力。对CB-NPs 20进行了系统的药代动力学、生物分布和体内疗效评估，这可能为药物筛选和临床应用提供显著指导。版权所有©2023 Elsevier B.V.。保留所有权利。

Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential in synergistic cancer therapy. However, it is still unclear how the nanoparticles' formula, such as injection dose, active agent ratio, and drug loading content, affects the side effects and in vivo efficacy of CB-NPs. In this study, a series of CB-NPs with different BLZ945/CA4 (B/C) ratios and drug loading contents were synthesized and evaluated on a hepatoma (H22) tumor-bearing mice model. The injection dose and B/C ratio were found to have a significant influence on the in vivo anticancer efficacy. The CB-NPs 20 with B/C weight ratio of 0.45/1, and total drug loading content (B + C) of 20.7 wt%, showed the highest potential for clinical application. Systematic pharmacokinetics, biodistribution, and in vivo efficacy evaluation for CB-NPs 20 have been finished, which may provide significant instruction for medicine screening and clinical application.Copyright © 2023 Elsevier B.V. All rights reserved.